Differential uptake of radiocopper labeled monocional antibody fragments and octreotide in the clearance organs has been correlated with the charge of the conjugated chelate (Anderson, et al.,J Nuci Med 1955; 36:850-858; Rogers, et al., J Lab Cmpd Radiopharm 1955; 37: 544-546). Hepatic and renal uptake has also been found for positively charged Cu-64 labeled azamacrocyclic ligands. We have compared the biodistributions of five Cu-64 complexes, TETA (-2 charge), 1,4.8,11-tetraazacyclotetradecane (cyclam), 1,4-ethano-1,4,8,11-tetraazacyclotetradecane (et-cyclam) (Jones-Wilson, et a., J Lab Cmpd Radiopharm 1955; 37: 462-464), 1,4,7.10-tetraazacyclododecane (cyclec) (each +2) and 1,4,7,10-tetraazacyclododecane-1,7-diacetic acid (DO2A) (neutral). Each complex was labeled in 100 % radiochemical purity as established by radio-TLC. Complex charge was established via electrophoresis at pH 7.34 and 5.45. Biodistribution, urine and blood metabolite studies were performed in female Sprague-Dawley rats. Renal clearance of Cu-64-TETA (-2) was rapid with greater than 80% of the activity in the bladder at 15 min post inj. However, each of the +2 complexes were retained in the kidney and liver to 24 hours post infection [%id/g: kidney cyclam (3.97+0.97), et-cyclam (4.19_0.42), cyclen (1.62+0.55); liver, cyclam (1.82+0.19), et-cyclam (1.65+0.36), cyclen (0.65+0.02)]. Analysis of urine samples indicated that each charged complex was excreted intact at all time points. Liver and kidney uptake was found for Cu-64-DO2A [15 min post in]: kidney (4.71+0.41), liver (1.51+0.16)], for the neutral complex. Renal activity decreased while hepatic activity remained constant over 24 hours [kidney (2.5+0.31), liver (1.38+0.14). Analysis of urine samples showed partial metabolism of the complex to several less polar species. The data indicate that the overall charge of the metal-ligand complex affects the clearance characteristics; therefore, chelate charge should be considered in the design of all metal based radiopharmaceuticals.